Janowski Michał, Ulańczyk Zofia, Łuczkowska Karolina, Sobuś Anna, Rogińska Dorota, Pius-Sadowska Ewa, Gniot Michał, Kozłowski Krzysztof, Lewandowski Krzysztof, Helbig Grzegorz, Machaliński Bogusław, Paczkowska Edyta
Department of Hematology and Transplantology, Pomeranian Medical University, Szczecin, Poland.
Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
Onco Targets Ther. 2022 Oct 10;15:1123-1141. doi: 10.2147/OTT.S371847. eCollection 2022.
The aim of our research was to investigate changes in the molecular background of the immune response in the chronic phase (CP) of chronic myeloid leukaemia (CML) during treatment with tyrosine kinase inhibitors (TKIs).
Global gene and miRNA expression profiles were assessed using genome-wide RNA and miRNA microarray technology in bone marrow mononuclear cells. Fifty-one patients were recruited, and bone marrow samples were taken at diagnosis before treatment with TKIs and after 3, 6, and 12 months of treatment with TKIs. The largest number of upregulated genes was observed when the 0-month group (time of diagnosis) was compared to the 3-month group; 1774 genes were significantly upregulated, and 390 genes were significantly downregulated.
Upregulated biological processes according to gene ontology (GO) classification involved basic cellular processes such as cell division, cell cycle, cell-cell adhesion, protein transport, mitotic nuclear division, apoptosis, and DNA replication. Differentially expressed miRNAs were annotated using GO classification to several immunity-related processes, including the T cell receptor signalling pathway, T cell costimulation, immune response, and inflammatory response. TKI therapy exerts a significant impact on cellular cycle processes and T-cell activation, which was proven at the molecular level.
我们研究的目的是调查慢性髓性白血病（CML）慢性期（CP）在接受酪氨酸激酶抑制剂（TKIs）治疗期间免疫反应分子背景的变化。
使用全基因组RNA和miRNA微阵列技术评估骨髓单个核细胞中的全局基因和miRNA表达谱。招募了51名患者，在诊断时、接受TKIs治疗前以及治疗3、6和12个月后采集骨髓样本。将0个月组（诊断时间）与3个月组进行比较时，观察到上调基因数量最多；1774个基因显著上调，390个基因显著下调。
根据基因本体（GO）分类，上调的生物学过程涉及基本细胞过程，如细胞分裂、细胞周期、细胞间粘附、蛋白质转运、有丝分裂核分裂、细胞凋亡和DNA复制。使用GO分类将差异表达的miRNA注释到几个与免疫相关的过程，包括T细胞受体信号通路、T细胞共刺激、免疫反应和炎症反应。TKI治疗对细胞周期过程和T细胞激活有显著影响，这在分子水平上得到了证实。
